4α,6-Dihydroxy-2α-hydroxy-methyl-3β-tetrahydropyran acetic acid γ lactone derivatives

ABSTRACT

The present specification provides novel intermediates and novel processes for the synthesis of Thromboxane B 2  11a-homo-11a-oxa-PGF 2 α), its 15-epimer, and various carboxyl derivatives thereof. In particular, there are disclosed various bicyclic tetrahydrofuran-containing lactones useful in the above processes, and corresponding acyclic lactones.

The present application is a divisional application of Ser. No. 686,893,filed Apr. 14, 1976, issued as U.S. Pat. No. 4,048,194 on Sept. 13,1977.

The present invention relates to Thromboxane B₂ and associatedintermediates and processes for which the essential materialconstituting disclosure therefor is incorporated by reference here fromSer. No. 676,890, filed Apr. 14, 1976, issued as U.S. Pat. No. 4,020,173on Apr. 26, 1977.

I claim:
 1. A thromboxane intermediate of the formula ##STR1## whereinR₃₁ is a hydroxy-hydrogen replacing group selected from the groupconsisting of R₉, R₁₀, and R₃₄ ;wherein R₉ is an acyl protecting groupselected from the group consisting of(a) benzoyl; (b) benzoylsubstituted with one to 5 alkyl of one to 4 carbon atoms, inclusive,phenylalkyl of 7 to 12 carbon atoms, inclusive, or nitro, with theproviso that not more than 2 substituents are other than alkyl, and thatthe total number of carbon atoms in the substituents does not exceed 10carbon atoms, with the further proviso that the substituents are thesame or different. (c) benzoyl substituted with alkoxycarbonyl of 2 to 5carbon atoms, inclusive; (d) naphthoyl; (e) naphthoyl substituted withone to 9, inclusive, alkyl of one to 4 carbon atoms, inclusive,phenylalkyl of 7 to 10 carbon atoms, inclusive, or nitro, with theproviso that not more than 2 substituents on either of the fusedaromatic rings are other than alkyl and that the total number of carbonatoms in the substituents on either of the fused aromatic rings does notexceed 10 carbon atoms, with the further proviso that the varioussubstituents are the same or different; and (f) alkanoyl of 2 to 12carbon atoms, inclusive; Wherein R₁₀ is a blocking group selected fromthe group consisting of(a) tetrahydropyranyl; (b) tetrahydrofuranyl; and(c) a group of the formula

    --C(OR.sub.11)(R.sub.12)--CH(R.sub.13)(R.sub.14),

wherein R₁₁ is alkyl of one to 18 carbon atoms, inclusive, cycloalkyl of3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms,inclusive, phenyl or phenyl substituted with one to 3 alkyl of one to 4carbon atoms, inclusive, wherein R₁₂ and R₁₃ are alkyl of one to 4carbon atoms, inclusive, phenyl, phenyl substituted with one, 2, or 3alkyl of one to 4 carbon atoms, inclusive, or when R₁₂ and R₁₃ are takentogether --(CH₂)_(a) -- or --(CH₂)_(b) --O--(CH₂)_(c), wherein a is 3,4, or 5, or b is one, 2, or 3, and c is one, 2, or 3, with the provisothat b plus c is 2, 3, or 4, with the further proviso that R₁₂ and R₁₃may be the same or different, and wherein R₁₄ is hydrogen orphenyl;wherein R₃₄ is an arylmethyl hydroxy-hydrogen replacing groupselected from the group consisting of (a) benzyl, (b) benzyl substitutedby one to five alkyl of one to four carbon atoms, inclusive, chloro,bromo, iodo, fluoro, nitro, phenylalkyl of 7 to 12 carbon atoms,inclusive, with the further proviso that the various substituents arethe same or different, (c) benzhydryl, (d) benzhydryl substituted by oneto ten alkyl of one to four carbon atoms, inclusive, chloro, bromo,iodo, fluoro, nitro, phenylalkyl of 7 to 12 carbon atoms, inclusive, (e)trityl, and (f) trityl substituted by one to 15 alkyl of one to fourcarbon atoms, inclusive, chloro, bromo, iodo, fluoro, nitro, phenylalkylof 7 to 12 carbon atoms, inclusive. 2.4α,6-Dihydroxy-2β-benzoyloxymethyl-3α-tetrahydropyranlacetic acidγ-lactone, or its 2α-epimer, thromboxane intermediates according toclaim 1.